Review concludes that specific recommendations are needed to harmonise the provision of fresh mother's milk to their preterm infants.

AIM: There are no specific recommendations for using a mother's fresh milk for her preterm infant. We reviewed the available evidence on its collection, storage and administration. METHODS: The working group of the French Neonatal Society on fresh human milk use in preterm infants searched the MEDLINE database and Cochrane Library up to June 2017 for papers published in English or French. They specifically analysed 282 papers providing information on prospective, retrospective and clinical studies and examined guidelines from various countries. RESULTS: The review concluded that fresh mother's own milk should be favoured in accordance with the latest recommendations. However, it must be carried out under stringent conditions so that the expected benefits are not offset by risks related to different practices. The working group has summarised the best conditions for feeding preterm infants with human milk, balancing high nutritional and immunological quality with adequate virological and bacteriological safety. Professionals must provide parents with the necessary conditions to establish breastfeeding, together with specific and strong support. CONCLUSION: Based on their review, the working group has made specific recommendations for using fresh mother's own milk under careful conditions, so that the expected benefits are not offset by risks related to practices.

Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition.

The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of Paediatric Gastroenterology and Nutrition in 1987 has made a new guideline necessary. Thus, an ad hoc expert panel was convened by the Committee on Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480), is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines, 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infant's own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate.

[Feeding during the first months of life and prevention of allergy]. / Alimentation des premiers mois de vie et prévention de l'allergie.

Allergy consists in the different manifestations resulting from immune reactions triggered by food or respiratory allergens. Both its frequency and severity are increasing. The easiest intervention process for allergy prevention is the reduction of the allergenic load which, for a major allergen such as peanuts, has to begin in utero. The primary prevention strategy relies first on the detection of at risk newborns, i.e. with allergic first degree relatives. In this targeted population, as well as for the general population, exclusive breastfeeding is recommended until the age of 6 months. The elimination from the mother's diet of major food allergens potentially transmitted via breast milk may be indicated on an individual basis, except for peanut, which is systematically retrieved. In the absence of breastfeeding, prevention consists in feeding at-risk newborns until the age of 6 months with a hypoallergenic formula, provided that its efficiency has been demonstrated by well-designed clinical trials. Soy based formulae are not recommended for allergy prevention. Complementary feeding should not be started before the age of 6 months. Introduction of egg and fish into the diet can be made after 6 months but the introduction of potent food allergens (kiwi, celery, crustaceans, seafood, nuts, especially tree nuts and peanuts) should be delayed after 1 year. This preventive policy seems partially efficacious on early manifestations of allergy but does not restrain the allergic march, especially in its respiratory manifestations. Probiotics, prebiotics as well as n-3 fatty polyunsaturated acids have not yet demonstrated any definitive protective effect.

[Folic acid and prevention of neural tube closure defects: the question is not solved yet]. / Prévention par l'acide folique des défauts de fermeture du tube neural: la question n'est toujours pas réglée.

Between 1981 and 1996, several interventional studies proved the efficacy of periconceptional folic acid supplementation in the prevention of neural tube closure defects (NTCD), first in women at risk (with a previous case of NTCD) and also in women of the general population in age to become pregnant. The poor observance of this supplementation led several countries (USA, Canada, Chile...) to decide mandatory folic acid fortification of cereals, which permitted a 30% (USA) to 46% (Canada) reduction in the incidence of NTCD. Moreover, this benefit was accompanied by a diminished incidence of several other malformations and of stroke and coronary accidents in elderly people. However, several papers drew attention to an increased risk of colorectal and breast cancer in relation with high blood folate levels and the use of folic acid supplements. A controlled interventional study showed a higher rate of recurrence of colic adenomas and a higher percentage of advanced adenomas in subjects receiving 1mg/day of folic acid. A recent study demonstrated an abrupt reversal of the downward trend in colorectal cancer 1 year after the beginning of cereal folic acid fortification in the USA and Canada. Two studies also reported impaired cognitive functions in elder persons with defective vitamin B(12) status. Taken in aggregate, these studies question the wisdom of a nationwide, mandatory, folic acid fortification of cereals. As of today, despite their limited preventive efficacy, a safe approach is to keep our current French recommendations and to increase the awareness of all caregivers, so as to improve the observance of these recommendations.

Nuclear DNA origin of mitochondrial complex I deficiency in fatal infantile lactic acidosis evidenced by transnuclear complementation of cultured fibroblasts.

We have studied complex I (NADH-ubiquinone reductase) defects of the mitochondrial respiratory chain in 2 infants who died in the neonatal period from 2 different neurological forms of severe neonatal lactic acidosis. Specific and marked decrease in complex I activity was documented in muscle, liver, and cultured skin fibroblasts. Biochemical characterization and study of the genetic origin of this defect were performed using cultured fibroblasts. Immunodetection of 6 nuclear DNA-encoded (20, 23, 24, 30, 49, and 51 kDa) and 1 mitochondrial DNA-encoded (ND1) complex I subunits in fibroblast mitochondria revealed 2 distinct patterns. In 1 patient, complex I contained reduced amounts of the 24- and 51-kDa subunits and normal amounts of all the other investigated subunits. In the second patient, amounts of all the investigated subunits were severely decreased. The data suggest partial or extensive impairment of complex I assembly in both patients. Cell fusion experiments between 143B206 rho degrees cells, fully depleted of mitochondrial DNA, and fibroblasts from both patients led to phenotypic complementation of the complex I defects in mitochondria of the resulting cybrid cells. These results indicate that the complex I defects in the 2 reported cases are due to nuclear gene mutations.

[Renal tubular dysgenesis and mutation in the renin gene]. / Dysgénésie tubulaire proximale et mutation du gène de la rénine.

Renal tubular dysgenesis is a severe and rare disorder of the renal development characterized by fetal anuria, oligohydramnios and early death from pulmonary hypoplasia and refractory arterial hypotension. We report on a female patient who presented with anuria in the neonatal period, requiring peritoneal dialysis until 5 months of age with unexpected diuresis recovery at 2 months of age. Clinical, histological and pathophysiological issues are discussed for this disease related to a mutation in the renin gene.

[Compliance with a protocol of prevention of neonatal group B streptococcal sepsis in the Aurore perinatal network]. / Application d'un protocole de prévention de l'infection materno-foetale à streptocoque B hémolytique au sein du réseau périnatal Aurore.

OBJECTIVE: Our purpose was to measure the compliance with the network hospitals protocol for preventing neonatal group B streptococcal sepsis. MATERIALS AND METHOD: All vaginal deliveries during a one-week period in 37 maternities of the perinatal network were reviewed retrospectively. RESULTS: A total of 752 records were reviewed. Compliance with the protocol regarding the time of culture was 91.1%. Overall, prevalence of group B streptococcal carriage was 14.2%. Among patients eligible for intrapartum antibiotics, 46.4% received adequate prophylaxis. Considering the length of labor, one out of two patients could have received intrapartum adequate antibiotics. Regarding newborns, 86.1% received adequate medical surveillance. There was no confirmed case of group B streptococcal sepsis during the week of study. CONCLUSION: All the maternities of network Aurore accepted and adopted evaluation principle. Some elements of protocol could be better applied, in particular delivering adequate intrapartum antibiotic prophylaxis.

Functional hypersomatotropism in small for gestational age (SGA) newborn infants.

Basal plasma GH levels and the GH responses to an injection of 1 microgram/kg 1-44(NH2) GHRH were determined on day 3 postnatally in 5 small gestational age (SGA) twin newborns and their appropriate gestational age (AGA) co-twins, and in 10 SGA singleton newborns and 6 AGA singleton newborns. The mean basal plasma GH level was higher in the SGA than in the AGA infants but the difference was significant only for singleton newborns (p less than 0.01). The mean peak plasma GH level was markedly increased in SGA compared to AGA infants (p less than 0.05 for twins, p less than 0.01 for singletons). Twelve SGA infants re-tested at 1 month had lower basal and peak plasma GH levels (p less than 0.001 and p less than 0.01). In 21 SGA and 17 AGA infants, serum IGF-I, measured by RIA between 12 and 96 hours after birth, was significantly higher in SGA than in AGA (p less than 0.001). These results suggest that, whatever the mechanism, functional hypersomatotropism is present at day 3 in SGA infants. This hypersomatotropism may participate in the early catch-up growth process.

Hypoparathyroidism during pregnancy: treatment with calcitriol.

A pregnant woman suffering from idiopathic hypoparathyroidism was treated with calcitriol [0.5-2 micrograms/day 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3)]. Her twin infants were delivered by cesarian section at 37 weeks of gestation. Laboratory investigations in the perinatal period disclosed: 1) normal serum calcium and phosphorus levels in the mother, 2) normal babies with no clinical or biochemical signs of hyperparathyroidism, 3) a low serum level of 25-hydroxyvitamin D despite a normal serum level of 1,25-(OH)2D in the mother, and 4) a low level of 25-hydroxyvitamin D and a high level of 1,25-(OH)2D in cord serum in both infants. It is suggested that calcitriol is an effective treatment of hypoparathyroidism during pregnancy and produces no ill effects on the baby.

Net calcium absorption in premature infants: results of 103 metabolic balance studies.

Net calcium absorption was evaluated in 103 low-birth-weight preterm infants by a 72-h balance technique. At birth the infants had a mean (+/- SE) gestational age of 30.9 +/- 0.2 wk and weighed 1.43 +/- 0.03 kg. When tested 3 wk later, their net calcium absorption averaged 58 +/- 1% with an intake of 80 +/- 2 mg Ca.kg body wt-1.d-1. Of the 103 infants, 58 had been fed low-birth-weight formulas supplemented with vitamin D. The remainder received banked human milk, of whom 34 were supplemented with vitamin D and calcium; 11 infants received no supplementation. Calcium absorption in the four subgroups did not differ significantly, with neither vitamin D supplementation nor supplementation with vitamin D and calcium affecting percent absorption significantly. Net calcium absorption was a linear function of intake (40-130 mg Ca.kg body wt-1.d-1) with a zero intercept. Because vitamin D supplementation did not increase net calcium absorption, it is concluded that in preterm low-birth-weight infants calcium absorption proceeds by a nonsaturable route, with the transcellular, vitamin D-regulated mechanism not yet expressed.

Estimating resting energy expenditure by simple lean-body-mass indicators in children on total parenteral nutrition.

The aim of this study was to determine simple predictive factors of the resting energy expenditure (REE) in children. Two groups, A (n = 14) and B (n = 23), were defined by their weight-for-height index, less than 90% and greater than 90%, respectively. Anthropometrically assessed lean body mass (LBM), 24-h urinary creatinine, and REE were measured. From multiple-regression analysis, the best-fitting equation for calculating REE (REE = 54.4 LBM (kg) + 0.095 creatinine (mmol/kg) + 4.7) was highly significant (r = 0.987, p less than 0.0001). Although the regressions of REE on weight were significantly different between the two groups, the equations using LBM or 24-h urinary creatinine did not discriminate between them. These findings suggest that an equation based on LBM or 24-h urinary creatinine excretion could be a more accurate estimate of REE than are conventional methods based on weight or height, and it may be applicable to diverse nutritional states.

Dietary composition and macronutrient storage in preterm infants.

A comparison has been made of the influence of feeding own mother's milk and formula on the oxidation and accretion of energy and macronutrients in the growing preterm infant of very low birth weight (less than 1,300 g) by using the combined techniques of nutrient balance and computerized indirect calorimetry. There were 22 studies in formula-fed infants and 15 studies in premature infants fed own mother's milk. Despite their lower metabolizable energy intake, the infants fed own mother's milk grew in weight, length, and head circumference at a rate approximating those of the formula-fed group. The metabolic rate was significantly lower in the infants fed own mother's milk (56.0 +/- 0.9 v 62.6 +/- 0.8 kcal/kg/d; P less than .001). The protein intake, oxidation, and accretion were similar in the two groups. The infants fed own mother's milk had a significantly lower fat intake (P less than .001), higher fat oxidation (P less than .025) and consequently lower fat accretion (P less than .001) than the formula-fed infants. The proportional fat content of the daily weight gain was lower in the infants fed own mother's milk (16% v 33%; P less than .001) but protein content was similar (13% v 12%). The accretion of energy, fat, and protein correlated with the respective metabolizable intakes in both groups (r = .81 to .98; P less than .001), suggesting that accretion rates and hence composition of weight gain are dependent on levels of energy and macronutrient intake.

Partition of energy metabolism and energy cost of growth in the very low-birth-weight infant.

Energy requirements are partitioned between needs for maintenance (including resting metabolism, thermoregulation, and muscular activity) and needs for synthesis and storage of new tissue. The partition of energy utilization was evaluated by 22 metabolic and nutritional balance studies in 13 formula-fed (SMA 20/24), growing, appropriate-for-gestational age, very low-birth-weight infants (mean +/- SE birth weight, 1,155 +/- 39 gm; study weight, 1,271 +/- 60 gm; age at study, 21 +/- 2 days; weight gain, 16.8 +/- 1 gm/kg/day). Continuous open-circuit, indirect calorimetry was performed for periods of 6 +/- 0.25 hours in a thermoneutral environment. Results expressed as mean kilocalories per kilogram per day (+/- SE) were: energy intake, 148.6 (+/- 3.9); stool and urine losses, 18.2 (+/- 1.5); metabolizable energy, 130.4 (+/- 3.5); "basal" metabolic rate, 47.0 (+/- 0.75); energy cost of activity, 4.3 (+/- 0.9); thermic effect of food, 11.3 (+/- 0.65); energy stored in new tissue, 67.8 (+/- 3.0). These results provide a partition of energy utilization in very low-birth-weight infants under thermoneutral conditions. Increased activity and a thermal environment outside the neutral range will augment maintenance energy requirements, thus decreasing the amount of energy available for growth if metabolizable energy intake remains constant. The energy cost of growth (ie, for synthesis of, and storage in, new tissue) was determined as 4.9 kcal/gm of weight gain. To attain the equivalent rate of intrauterine weight gain, a metabolizable energy intake of approximately 60 kcal/kg/day in excess of maintenance requirements of 51.3 kcal/dk/day must be provided.

Development of cochlear active mechanisms in humans differs between gender.

Despite onset of function early during the third term of gestation, the human auditory system demonstrates continued maturation, thought previously to occur primarily at the neural level. The electromotile properties of outer hair cells appear to contribute substantially to hearing sensitivity and frequency selectivity and lead to the generation of otoacoustic emissions (OAEs). This report demonstrates continued development of cochlear active mechanisms (i.e. end-organ level) after onset of cochlear function, as reflected by OAEs. Significant gender differences also are reported, corresponding to recently observed intersex differences in cochlear length and precursory to gender differences observed in the adult.

Continuous insulin infusion in hyperglycaemic very-low-birth-weight infants receiving parenteral nutrition.

Continuous infusion of insulin was used to improve glucose tolerance in 30 premature (26.4+/-1.4 weeks) very-low-birth-weight (750+/-211.3 g) hyperglycaemic infants receiving parenteral nutrition. Infusion of insulin was started at 159.1+/-67 h of life; while glycaemia was 12.1+/-3.3 mmol/l. Normoglycaemia was restored within 31.4h (range 2-134 h). A maximum insulin dose of 0.4 (range 0.07-4.2)IU/kg/h was required to control the blood glucose, the mean cumulative doses of insulin required was 3.27 IU/kg (range 0.09-18.1). The mean glucose infusion rate during insulin treatment was 20.3+/-1.7 g/kg/day; lipid was 4.6+/-1.1 g/kg/day and non-protein caloric intake 121.7+/-16.5 kcal/kg/day. Infants reach 85 kcal/kg/day of non-protein energy intake at 179.5+/-71.2 h after birth. During continuous insulin infusion, enteral feeding was started in all infants at 124.9+/-75.8 h of life. Insulin was continued for 317.7+/-196.6 h. Only two infants lost weight during the first week of treatment, the remaining infant gained weight steadily. In conclusion, continuous insulin infusion can rapidly and safely improve intravenous glucose tolerance, allowing higher caloric intake and growth in very-low-birth-weight infants who develop hyperglycaemia during total parenteral nutrition.

Oxygen consumption during sleep in children under continuous and cyclic nutrition.

The present study investigated the effects of two modalities of parenteral nutrition (continuous nutrition over the 24-hour period vs. cyclic nutrition, i.e., administered only during the night) on O2 consumption during sleep in children affected by severe gastrointestinal diseases. In both feeding modalities O2 consumption was always highest in REM sleep, intermediate in stage 2 and lowest in SWS. The trends during the night of O2 consumption (an increase from the second to the third part of the night) for different sleep stages were comparable in both feeding modalities. These results suggest that O2 consumption is not affected by the feeding modalities investigated, but is dependent on both sleep stages and time of night.

Nutritional evaluation of protein hydrolysate formulas.

Growth parameters, biochemical indice of protein metabolism and plasma Amino acid (AA) concentrations were investigated during the first month of life in term infants (n = 61) fed various protein hydrolysate formulas (whey (WHF, n = 3), soy collagen (SCHF, n = 1) and whey-casein hydrolysate formulas (WCHF, n = 1)). In addition, metabolic balance studies were performed in 10 infants fed WHF and in 5 fed WCHF. Comparatively to breast fed infants, growth reduction and decrease in plasma protein concentrations were observed with the use of one of the WHF and in a lesser extent with the SCHF and the WCHF. Plasma amino acid pattern reflected the AA content of the formulas. Whey hydrolysate formulas induced mainly an increase in threonine and a decrease in tyrosine concentrations. Soy-collagen hydrolysate formula led to an increase of non-essential amino acids, such as glycine and hydroxyproline and a decrease in plasma lysine and cystine. Whey-casein hydrolysate formula induced a plasma amino acid pattern close to the profile observed in breast fed infant. Metabolic balance studies showed a relative reduction in nitrogen absorption and utilisation in the infants fed the WHF and the WCHF. In addition a drastic reduction in fat, calcium and phosphorus absorption was also observed with the use of the WCHF. In preterm infants (n = 19) fed whey predominant hydrolysed preterm formulas (n = 3), metabolic balance studies an plasma AA concentration were evaluated at the end of the first month of life at 34 weeks of gestation age. Comparatively to similar preterm infants fed conventional preterm formulas, a relative reduction in nitrogen absorption (83% vs 90%) and retention (64 vs 70%) as well as in phosphorus absorption (78 vs 89%) was observed. Calcium retention was similar (48 vs 45 mg/kg/d) but calcium intake was significantly higher in infants fed hydrolysate formulas 120 vs 91 mg/kg/d. Plasma amino acid concentrations were related to amino acid composition of the formulas. Compared with the standard preterm formulas, all three protein hydrolysate formulas led to a significant increase in plasma threonine and a decrease in tyrosine and phenylalanine concentrations. In addition, there was a reduction in plasma histidine, valine, leucine, cystine, methionine and/or tryptophane with some of the hydrolysate formulas used. In conclusion, these studies provide evidence that protein hydrolysed formulas are not equivalent to whole protein formulas in terms of nutritional efficiency for preterm and term infants. Therefore further extensive nutritional studies on growth, biochemical indices of protein metabolism and metabolic balance, including minerals and trace elements, appear to be necessary before maintaining and promoting the use of such formulas for teh potential benefits on atopic disease in preterm and in full-term newborn infants.

Spontaneous otoacoustic emissions in preterm neonates: prevalence and gender effects.

A number of lines of evidence indicate that the human cochlea is fully functional as a mature sound transducer by 6 months of age. However, information about the development of the active cochlear mechanisms and notably the development of outer hair cell (OHC) activity is yet incomplete. Recording and analysis of otoacoustic emissions (OAEs), probably generated by the OHCs of the organ of Corti, have led to a better understanding, in humans, of how sounds are analysed in the cochlea by means of active mechanisms. Evoked OAEs (EOAEs) and spontaneous OAEs (SOAEs), when they can be recorded in full-term and preterm neonates, show different characteristics from those in adults, suggesting that maturation of the peripheral auditory system is incomplete at birth. To learn more about this maturation, using the best-established facts concerning SOAEs in adults, such as their greater prevalence in females and also in right ears, SOAEs were studied in more detail in 81 preterm neonates, from 30 to 40 weeks of conceptional age, all presenting bilateral EOAEs according to objective criteria. The first finding of this study was that SOAEs existed and could be recorded as of 30 weeks of conceptional age in humans. Some SOAE characteristics in preterm neonates, such as prevalence, peak number and acoustic frequencies, showed similarity with full-term neonates. Comparison of other criteria between the two populations, such as greater SOAE prevalence in right ears and higher SOAE peak number in females, suggested that these developmental factors emerge around term in humans. Comparison of SOAE characteristics between male and female preterms suggested that male preterms were less advanced in peripheral auditory development than were female preterms.

Type of initial brainstem auditory evoked potentials (BAEP) impairment and risk factors in premature infants.

Brainstem auditory evoked potentials (BAEPs) were recorded in 89 premature infants aged between 34 and 52 weeks. 47.2% had normal and 52.8% abnormal BAEPs in at least one ear. Seven risk factors were taken into account: birth weight lower than 1500 g, hypoxia, neurological damage, fetal pathology, associated malformation, the use of ototoxic drugs, and exchange transfusion. The type of BAEP impairment was defined as either endocochlear, transmission or retrocochlear damage. Percentage BAEP impairment was higher in case of hypoxia (63.3%) but remained similar whether the other risk factors were present or absent. Transmission impairment was more frequent in case of birth weight lower than 1500 g, hypoxia or ototoxic drug administration; Endocochlear damage occurred more frequently when ototoxic drugs had been used or exchange transfusion performed. When birth weight was lower than 1500 g, transmission damage was more frequent than when birth weight was higher than 1500 g. In contrast, endocochlear damage was more frequent when birth weight was higher than compared with lower than 1500 g. In male infants, BAEP impairment was more frequent and more often of retrocochlear type than in female infants. BAEP impairment was more frequently of endocochlear type in female compared to male infants. Among the 89 premature infants recorded, 11.2% has endocochlear damage corresponding to potentially handicapping hearing loss. These results are discussed with reference to the literature.

Non-linear patterns of growth in very low birth weight infants.

The deviations of daily weight, weekly length and head circumference from linear growth were analyzed in 87 very low birth weight infants. The deviations exhibited a highly significant polynomial oscillation not only for weight, but also for length and head circumference. The weight amplitudes were larger for males than for females. They were also larger in infants appropriate for gestational age than in small-for-date infants. The difference with trophicity may be related to the process of adjustment of catch-up in small-for-date infants. However, the mechanisms of these oscillatory deviations could also be explained by clinical events, method of feeding, or homeostatic regulation. Further studies are required to elucidate the role of the different factors. Am. J. Hum. Biol. 10:637-646, 1998. © 1998 Wiley-Liss, Inc.